Are there socioeconomic inequalities in polypharmacy among older people? A systematic review and meta-analysis

Background: Socioeconomic status (SES) may influence prescribing, concordance and adherence to medication regimens. This review set out to investigate the association between polypharmacy and an individual’s socioeconomic status. Methods: A systematic review and meta-analyses of observational studies was conducted across four databases. Older people (≥ 55 years) from any healthcare setting and residing location were included. The search was conducted across four databases: Medline (OVID), Web of Science, Embase (OVID) and CINAHL. Observational studies from 1990 that reported polypharmacy according to SES were included. A random-effects model was undertaken comparing those with polypharmacy (≥ 5 medication usage) with no polypharmacy. Unadjusted odds ratios (ORs), 95% confidence intervals (CIs) and standard errors (SE) were calculated for each study. Results: Fifty-four articles from 13,412 hits screened met the inclusion criteria. The measure of SES used were education (50 studies), income (18 studies), wealth (6 studies), occupation (4 studies), employment (7 studies), social class (5 studies), SES categories (2 studies) and deprivation (1 study). Thirteen studies were excluded from the meta-analysis. Lower SES was associated with higher polypharmacy usage: individuals of lower educational backgrounds displayed 21% higher odds to be in receipt of polypharmacy when compared to those of higher education backgrounds. Similar findings were shown for occupation, income, social class, and socioeconomic categories. Conclusions: There are socioeconomic inequalities in polypharmacy among older people, with people of lower SES significantly having higher odds of polypharmacy. Future work could examine the reasons for these inequalities and explore the interplay between polypharmacy and multimorbidity

Clinical and cost effectiveness of endoscopic bipolar radiofrequency ablation for the treatment of malignant biliary obstruction: a systematic review

BACKGROUND: Early evidence suggests that using radiofrequency ablation as an adjunct to standard care (i.e. endoscopic retrograde cholangiopancreatography with stenting) may improve outcomes in patients with malignant biliary obstruction. OBJECTIVES: To assess the clinical effectiveness, cost-effectiveness and potential risks of endoscopic bipolar radiofrequency ablation for malignant biliary obstruction, and the value of future research. DATA SOURCES: Seven bibliographic databases, three websites and seven trials registers were searched from 2008 until 21 January 2021. REVIEW METHODS: The study inclusion criteria were as follows: patients with biliary obstruction caused by any form of unresectable malignancy; the intervention was reported as an endoscopic biliary radiofrequency ablation to ablate malignant tissue that obstructs the bile or pancreatic ducts, either to fit a stent (primary radiofrequency ablation) or to clear an obstructed stent (secondary radiofrequency ablation); the primary outcomes were survival, quality of life or procedure-related adverse events; and the study design was a controlled study, an observational study or a case report. Risk of bias was assessed using Cochrane tools. The primary analysis was meta-analysis of the hazard ratio of mortality. Subgroup analyses were planned according to the type of probe, the type of stent (i.e. metal or plastic) and cancer type. A de novo Markov model was developed to model cost and quality-of-life outcomes associated with radiofrequency ablation in patients with primary advanced bile duct cancer. Insufficient data were available for pancreatic cancer and secondary bile duct cancer. An NHS and Personal Social Services perspective was adopted for the analysis. A probabilistic analysis was conducted to estimate the incremental cost-effectiveness ratio for radiofrequency ablation and the probability that radiofrequency ablation was cost-effective at different thresholds. The population expected value of perfect information was estimated in total and for the effectiveness parameters. RESULTS: Sixty-eight studies (1742 patients) were included in the systematic review. Four studies (336 participants) were combined in a meta-analysis, which showed that the pooled hazard ratio for mortality following primary radiofrequency ablation compared with a stent-only control was 0.34 (95% confidence interval 0.21 to 0.55). Little evidence relating to the impact on quality of life was found. There was no evidence to suggest an increased risk of cholangitis or pancreatitis, but radiofrequency ablation may be associated with an increase in cholecystitis. The results of the cost-effectiveness analysis were that the costs of radiofrequency ablation was £2659 and radiofrequency ablation produced 0.18 quality-adjusted life-years, which was more than no radiofrequency ablation on average. With an incremental cost-effectiveness ratio of £14,392 per quality-adjusted life-year, radiofrequency ablation was likely to be cost-effective at a threshold of £20,000 per quality-adjusted life-year across most scenario analyses, with moderate uncertainty. The source of the vast majority of decision uncertainty lay in the effect of radiofrequency ablation on stent patency. LIMITATIONS: Only 6 of 18 comparative studies contributed to the survival meta-analysis, and few data were found concerning secondary radiofrequency ablation. The economic model and cost-effectiveness meta-analysis required simplification because of data limitations. Inconsistencies in standard reporting and study design were noted. CONCLUSIONS: Primary radiofrequency ablation increases survival and is likely to be cost-effective. The evidence for the impact of secondary radiofrequency ablation on survival and of quality of life is limited. There was a lack of robust clinical effectiveness data and, therefore, more information is needed for this indication. FUTURE WORK:  Future work investigating radiofrequency ablation must collect quality-of-life data. Highquality randomised controlled trials in secondary radiofrequency ablation are needed, with appropriate outcomes recorded. STUDY REGISTRATION: This study is registered as PROSPERO CRD42020170233. FUNDING:  This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 7. See the NIHR Journals Library website for further project information

Selective Reduction of AMPA Currents onto Hippocampal Interneurons Impairs Network Oscillatory Activity

Reduction of excitatory currents onto GABAergic interneurons in the forebrain results in impaired spatial working memory and altered oscillatory network patterns in the hippocampus. Whether this phenotype is caused by an alteration in hippocampal interneurons is not known because most studies employed genetic manipulations affecting several brain regions. Here we performed viral injections in genetically modified mice to ablate the GluA4 subunit of the AMPA receptor in the hippocampus (GluA4HC−/− mice), thereby selectively reducing AMPA receptor-mediated currents onto a subgroup of hippocampal interneurons expressing GluA4. This regionally selective manipulation led to a strong spatial working memory deficit while leaving reference memory unaffected. Ripples (125–250 Hz) in the CA1 region of GluA4HC−/− mice had larger amplitude, slower frequency and reduced rate of occurrence. These changes were associated with an increased firing rate of pyramidal cells during ripples. The spatial selectivity of hippocampal pyramidal cells was comparable to that of controls in many respects when assessed during open field exploration and zigzag maze running. However, GluA4 ablation caused altered modulation of firing rate by theta oscillations in both interneurons and pyramidal cells. Moreover, the correlation between the theta firing phase of pyramidal cells and position was weaker in GluA4HC−/− mice. These results establish the involvement of AMPA receptor-mediated currents onto hippocampal interneurons for ripples and theta oscillations, and highlight potential cellular and network alterations that could account for the altered working memory performance

Emotion and location cues bias conceptual retrieval in people with deficient semantic control

Visuo-spatial context and emotional valence are powerful cues to episodic retrieval, but the contribution of these inputs to semantic cognition has not been widely investigated. We examined the impact of visuo-spatial, facial emotion and prosody cues and miscues on the retrieval of dominant and subordinate meanings of ambiguous words. Cue photographs provided relevant visuo-spatial or emotional information, consistent with the interpretation of the ambiguous word being probed, while miscues were consistent with an alternative interpretation. We compared the impact of these cues in healthy controls and semantic aphasia patients with deficient control over semantic retrieval following left-hemisphere stroke. Patients showed greater deficits in retrieving the subordinate meanings of ambiguous words, and stronger effects of cueing and miscuing relative to healthy controls. These findings suggest that contextual cues that guide retrieval to the appropriate semantic information reduce the need to constrain semantic retrieval internally, while miscues that are not aligned with the task increase the need for semantic control. Moreover, both valence and visuo-spatial context can prime particular semantic interpretations, in line with theoretical frameworks that argue meaning is computed through the integration of these features. In semantic aphasia, residual comprehension relies heavily on facial expressions and visuospatial cues. This has important implications for patients, their families and clinicians when developing new or more effective modes of communication

Differential predictors for alcohol use in adolescents as a function of familial risk

Abstract: Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions

Differential predictors for alcohol use in adolescents as a function of familial risk

Abstract: Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions

Collaborative Study of Trimtect®️ as a Plant Growth Regulator on Shrub Physiology and Drought Tolerance

Color poster with text, photographs, and graphs.Paclobutrazol is a synthetic plant growth regulator known to reduce the size of plants and improve drought tolerance in some species. Paclobutrazol blocks a key step in the formation of gibberellic acid (GA), a plant hormone that stimulates growth and development, therefore resulting in modified growth. Trimtect, a product made by Rainbow Treecare Scientific Advancements (Minneapolis, MN), incorporates paclobutrazol and is being formulated for commercial use, as some of the associated changes in growth are desirable from a landscaping maintenance point of view. However, a better understanding and record of physiological responses to Trimtect treatments are needed. Therefore, to better understand plant growth regulation, we partnered with Rainbow Treecare Scientific Advancements to study the effects of their current Trimtect formulation on the physiology of three common shrub species undergoing water stress. The information from this study is helping Rainbow Treecare Scientific Advancements refine formulations to improve their product for use in low maintenance landscapes.University of Wisconsin--Eau Claire Office of Research and Sponsored Program

COVID-19 Impact on Diagnostic Innovations: Emerging Trends and Implications

Diagnostic testing remains the backbone of the coronavirus disease 2019 (COVID-19) response, supporting containment efforts to mitigate the outbreak. The severity of this crisis and increasing capacity issues associated with polymerase chain reaction (PCR)-based testing, accelerated the development of diagnostic solutions to meet demands for mass testing. The National Institute for Health Research (NIHR) Innovation Observatory is the national horizon scanning organization in England. Since March, the Innovation Observatory has applied advanced horizon scanning methodologies and tools to compile a diagnostic landscape, based upon data captured for molecular (MDx) and immunological (IDx) based diagnostics (commercialized/in development), for the diagnosis of SARS-CoV-2. In total we identified and tracked 1608 diagnostics, produced by 1045 developers across 54 countries. Our dataset shows the speed and scale in which diagnostics were produced and provides insights into key periods of development and shifts in trends between MDx and IDx solutions as the pandemic progressed. Stakeholders worldwide required timely and detailed intelligence to respond to major challenges, including testing capacity and regulatory issues. Our intelligence assisted UK stakeholders with assessing priorities and mitigation options throughout the pandemic. Here we present the global evolution of diagnostic innovations devised to meet changing needs, their regulation and trends across geographical regions, providing invaluable insights into the complexity of the COVID-19 phenomena

Smallpox Vaccination of Laboratory Workers at US Variola Testing Sites

To evaluate the need to revaccinate laboratory workers against smallpox, we assessed regular revaccination at the US Laboratory Response Network’s variola testing sites by examining barriers to revaccination and the potential for persistence of immunity. Our data do not provide evidence to suggest prolonging the recommended interval for revaccination